International incidence patterns and migration studies, epidemiological data, and animal and in vitro studies suggest that high-fat diets rich in omega-6 fatty acids increase the risk of developing prostate cancer. The mechanisms by which dietary fat promotes prostate carcinogenesis are not completely known, thus complicating the identification of intermediate markers of activity or efficacy for dietary intervention. Recently, our laboratories have completed a series of studies demonstrating the ability of a low fat diet to inhibit the growth of human prostate cancer in a SCID mouse model, and the ability of omega-3 fatty acids to inhibit the growth of prostate cancer in vitro. In parallel, we have conducted two dietary intervention trials in humans in order to identify potential serum bioassays and serum and tissue biomarkers of the effects of low fat and high omega-3 fatty acid diets. Based on our prior studies, we hypothesize that serum and tissue biomarkers can be developed that correlate with anti-tumor activity and may serve as intermediate endpoints for large-scale prostate cancer prevention trials. To test this hypothesis we propose two Specific Aims: Aim 1. To evaluate the ability of a low fat diet high in omega-3 fatty acids to prevent prostate cancer and to correlate intermediate serum and tissue biomarkers/bioassays with dietary efficacy in pre-clinical models of prostate cancer. Aim 2. To validate the intermediate biomarkers from Aim I in a dietary intervention trial of men undergoing radical prostatectomy. The ultimate goals of our project are (1) to identify the most promising diet (vis a vis fat content) for future prevention trials and (2) to identify markers (particularly in serum) that correlate with dietary activity and may be useful as intermediate endpoints for these trials.